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Osteogenesis: the formation of bones

Osteogenesis is the biological process by which bones are formed . It begins during the eighth week of embryonic development, being also the process on which the repair of fractures depends.

Skeleton training and development

Osteogenesis: the formation of bones

All the bones of the human skeleton derive from three embryonic structures, resulting in three different lineages. These structures are the somites, the mesoderm and the neural crest. The process of osteogenesis consists, basically, in the transformation of preexisting tissue into bone tissue. There are two mechanisms:

  • Intramembranous ossification. This is the name that receives the direct transformation of the original tissue by bone tissue.
  • Endochondral ossification. This process is somewhat more complex and takes place in two stages. First, the initial tissue is replaced by cartilage , then the cartilage is ossified.

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Embryonic structures that give rise to bones

Somites are transient embryonic structures. Even so, they are fundamental for the development of the segmented structures characteristic of vertebrates. From the somites derive the bones that are part of the central axis of the body or axial skeleton. These are the bones of the skull and the auditory, the hyoid, the ribs, the sternum and the spine.

The mesoderm is one of the three cellular layers from which the whole embryo develops . Initially, there are three layers of cells: one outer, one intermediate and one internal. Thanks to a complex process of differentiation, each and every one of the structures of a human body develops from them. The mesoderm is the middle layer, and among many other structures, it gives rise to the bones of the extremities.

  Finally , the neural crest is a transient cell formation, typical of the early stages of development. It has a fundamental characteristic: the pluripotency of its cells. That is, the cells of the neural crest can give rise to almost any type of definitive structure of the body. With regard to the skeleton , they give rise to craniofacial bones, cartilage and other structures.

Intramembranous ossification process

Osteogenesis: the formation of bones

Through this process the flat bones of the skull are formed. As its name suggests, ossification occurs inside a membrane of connective tissue. Some of the cells in this membrane will become osteoblasts, the bone matrix forming cells. Others will do so in cells that are part of the small blood vessels that supply the bones.

The osteoblasts are grouped forming what is known as the ossification center , around which the bone will progressively form. These cells synthesize and release the necessary components to create a matrix capable of capturing calcium salts.

In this way, the initial membrane ossifies. The transformation of embryonic cells into osteoblasts occurs thanks to the activation of transcription factor CBFA1. In turn, the activation of CBFA1 depends on the BMP proteins.

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Endochondral ossification process

This other process is characterized by the formation of cartilage from embryonic tissue and subsequent ossification. For this, five stages are necessary:

  • The cells express two transcription factors: Pax 1 and Scleraxis. These factors are fundamental for the activation of the genes that will convert the original cells into cartilage. The expression of the transcription factors is possible thanks to the fact that some cells induce the neighboring ones in a paracrine manner.
  • Next, the cells that have expressed the necessary genes are grouped and converted into chondrocytes. During this process, the SOX9 gene is fundamental.
  • These chondrocytes multiply rapidly and form a kind of “mold” for the future bone.
  • In a fourth step, the multiplication stops and the chondrocytes increase in size. At this moment, in addition, they modify the components that they released for the formation of the matrix. In this way, the new matrix can calcify thanks to calcium carbonate.
  • Finally, the cartilage mold is traversed by the sagittal vessels in formation. The chondrocytes die progressively, being replaced by osteoblasts.

Osteoblasts and osteoclasts

Osteogenesis: the formation of bones

Unlike osteoblasts, osteoclasts are cells responsible for bone destruction. Its activity must always be in balance with the activity of the osteoblasts, since the correct formation of the bones depends on it.

Osteogenesis imperfecta: the disease of crystal bones

Osteogenesis imperfecta is a genetic disease, characterized by excessive weakness of the bones. People who suffer from it suffer fractures almost constantly, among other problems. Other associated problems are deafness, visual difficulties or constipation.

The disease is due to mutations that alter collagen I , an essential component in the bone matrix. The lack of this substance is responsible for the excessive fragility of the bones of those affected. The disease is very rare and the prognosis is very variable. The evolution of the disease, in general, depends on a large number of individual factors. In many cases it improves after adolescence.

Osteopetrosis: too dense bones

Osteogenesis: the formation of bones

Osteopetrosis is a rare congenital disease, characterized by a pathological increase in bone density . It is a consequence of an imbalance between the action of osteoblasts and osteoclasts. In most cases, due to mutations, the carbonic anhydrase of osteoclasts is altered, making them dysfunctional.

People with this disease, although it seems ironic, also suffer fractures. This is because, although the bone density is increased, the bones formed remain abnormal. Other symptoms that accompany it are pain and hemorrhages, growth retardation or repeated infections.

Bibliography

  1. Gilber SF . Osteogenesis: The development of Bones . In: Gilbert SF. Developmental Biology. 6 ed. Sunderland (MA) 2000

Osteogenesis: the formation of bones

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